TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20594	62005;62006;62007	chr2:178589945;178589944;178589943	chr2:179454672;179454671;179454670
N2AB	18953	57082;57083;57084	chr2:178589945;178589944;178589943	chr2:179454672;179454671;179454670
N2A	18026	54301;54302;54303	chr2:178589945;178589944;178589943	chr2:179454672;179454671;179454670
N2B	11529	34810;34811;34812	chr2:178589945;178589944;178589943	chr2:179454672;179454671;179454670
Novex-1	11654	35185;35186;35187	chr2:178589945;178589944;178589943	chr2:179454672;179454671;179454670
Novex-2	11721	35386;35387;35388	chr2:178589945;178589944;178589943	chr2:179454672;179454671;179454670
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-37
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.8274
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
L/P	None	None	0.873	N	0.344	0.208	0.620567169836	gnomAD-4.0.0	2.73781E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59859E-06	0	0
L/Q	None	None	0.029	N	0.279	0.142	0.497806138765	gnomAD-4.0.0	6.84452E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99646E-07	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
L/A	0.104	likely_benign	0.1133	benign	-0.377	Destabilizing	0.209	N	0.307	neutral	None	None	None	None	N
L/C	0.4822	ambiguous	0.5264	ambiguous	-0.644	Destabilizing	0.991	D	0.277	neutral	None	None	None	None	N
L/D	0.404	ambiguous	0.4292	ambiguous	-0.232	Destabilizing	0.39	N	0.336	neutral	None	None	None	None	N
L/E	0.1732	likely_benign	0.1769	benign	-0.336	Destabilizing	0.002	N	0.235	neutral	None	None	None	None	N
L/F	0.1601	likely_benign	0.1709	benign	-0.571	Destabilizing	0.818	D	0.287	neutral	None	None	None	None	N
L/G	0.3612	ambiguous	0.3931	ambiguous	-0.483	Destabilizing	0.561	D	0.367	neutral	None	None	None	None	N
L/H	0.2147	likely_benign	0.2208	benign	0.116	Stabilizing	0.901	D	0.273	neutral	None	None	None	None	N
L/I	0.0715	likely_benign	0.0691	benign	-0.227	Destabilizing	0.003	N	0.187	neutral	N	0.44846693	None	None	N
L/K	0.1599	likely_benign	0.1616	benign	-0.25	Destabilizing	0.007	N	0.191	neutral	None	None	None	None	N
L/M	0.0995	likely_benign	0.1035	benign	-0.458	Destabilizing	0.818	D	0.311	neutral	None	None	None	None	N
L/N	0.2169	likely_benign	0.2349	benign	-0.057	Destabilizing	0.818	D	0.358	neutral	None	None	None	None	N
L/P	0.182	likely_benign	0.2029	benign	-0.248	Destabilizing	0.873	D	0.344	neutral	N	0.4483495	None	None	N
L/Q	0.0995	likely_benign	0.0992	benign	-0.27	Destabilizing	0.029	N	0.279	neutral	N	0.446253344	None	None	N
L/R	0.1809	likely_benign	0.1837	benign	0.236	Stabilizing	0.326	N	0.373	neutral	N	0.4483495	None	None	N
L/S	0.1318	likely_benign	0.1439	benign	-0.428	Destabilizing	0.561	D	0.329	neutral	None	None	None	None	N
L/T	0.1078	likely_benign	0.119	benign	-0.431	Destabilizing	0.561	D	0.327	neutral	None	None	None	None	N
L/V	0.0696	likely_benign	0.0718	benign	-0.248	Destabilizing	0.003	N	0.173	neutral	N	0.439596731	None	None	N
L/W	0.3328	likely_benign	0.3534	ambiguous	-0.597	Destabilizing	0.991	D	0.32	neutral	None	None	None	None	N
L/Y	0.3594	ambiguous	0.368	ambiguous	-0.341	Destabilizing	0.901	D	0.284	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.